Retinoids and interferon-α (IFN-α) have been shown to have a synergetic antiproliferative and differentiative effect on many cell lines, and in combination they have already been tested with some success in the treatment of some tumors. We investigated the tolerance and efficacy of high dose 13-cis-retinoic acid (2 mg/kg/day) and IFN-α in the treatment of advanced squamous cell carcinoma of the lung and of the head and neck. No partial or complete response was observed in the 10 patients treated. The toxicity was unusual and mild to moderate considering the dose of retinoid given. This observation leads us to suspect that IFN-α may alleviate some of the side effects of the retinoid, and is of interest in the design of future clinical tri